Without limiting the scope of the invention, its background is described in connection with the field of in vivo cancer detection, more particularly, optical methods to intra-operatively detect cancer margins in prostate and kidney cancers.
Clinically localized prostate cancer is generally treated with either radiation therapy or surgery. Surgical treatment is currently undergoing a significant revolution; that is laparoscopic radical prostatectomy (LRP). This procedure permits complete removal of the prostate and seminal vesicles while minimizing pain and recovery. However, the laparoscopic approach greatly limits tactile sensation during the procedure. This is particularly true with robot-assisted LRP where no tactile feedback is available forcing the surgeon to rely solely on visual cues.
Kidney cancer is increasingly detected at very early stages due to the wide spread use of axial imaging for a variety of complaints. Associated with this stage migration is an increase in the incidence of benign histology associated with such tumors. In fact, 15-20% of renal tumors measuring less than 4 cm are benign. However, traditional diagnostic needle biopsy of small renal masses is not commonly performed due to its consistent and clinically unacceptable false negative rate. As such, nephron-sparing surgery (i.e. partial nephrectomy) is a preferred management technique for most small tumors. The advantage of this approach is that it preserves kidney function, especially in those cases of benign disease. However, both open and laparoscopic partial nephrectomies usually require renal ischemia to excise the tumors safely creating a unique, technically challenging procedure with significant time pressures to limit the renal insult. Of course, complete excision with a negative margin is required to minimize the risk of tumor recurrence but unfortunately, the surgeon cannot evaluate the surgical specimen until the procedure is completed and specimen extracted. Although intra-operative frozen section pathologic analysis of a few select tissue fragments from the resected specimen or renal parenchyma can be obtained, it is time consuming risking renal ischemic injury and costly. Furthermore, concrete conclusions based on such samples are unreliable, as they do not reflect the entire surgical margin status.
Kidney tumors are intraparenchymal tumors that are commonly malignant. For early clinically localized kidney tumors, it is not possible to reliably confirm benign versus malignant disease or identify the deep parenchymal tumor margin during surgery. Prostate cancer, on the other hand, is an intraparenchymal tumor that is commonly multifocal. For early clinically localized prostate cancer, it is also not possible to visually identify the tumor during surgery, either within the prostate or at its capsular margin. Because of this, it would be highly desirable to develop an optical spectroscopic approach that will allow the surgeon in real time percutaneously confirm a cancer or benign diagnosis, and, during surgical excision of confirmed malignancies, to detect renal carcinoma at the surgical margin during resection.
In recent years, varieties of optical spectroscopy techniques have been developed for detection and diagnosis of different kinds of cancers. However, most of these techniques mainly target luminal malignancies, such as cervical, colon, and esophageal cancers. For example, U.S. Pat. No. 6,912,412 discloses a plurality of spectroscopic systems and methods to measure characteristics of tissue useful in the diagnosis of disease. In the '412 patent, a combination of fluorescence, reflectance and light scattered spectra can be measured and processed to provide biochemical, architectural and morphological state of tissue. The methods and systems can be used particularly in the early detection of carcinoma within tissue in vivo and in vitro.
Another example is shown is U.S. Pat. No. 7,309,867 issued to Costa et al. Costa provides methods for determining the probability that a given region of a tissue sample contains tissue of a given category, such as CIN 1 (cervical intraepithelial neoplasia, grade 1), CIN 2/3 (cervical intraepithelial neoplasia grades 2 and/or 3), normal squamous, normal columnar, and metaplasia. The '867 patent provides increased diagnostic accuracy by combining a plurality of statistical classification techniques. Furthermore, it mentioned combining one or more statistical techniques with one or more non-statistical classification techniques.
One can also see an example shown in U.S. Pat. No. 7,282,723. The '723 patent discloses methods for processing tissue-derived spectral data for use in a tissue classification algorithm. Methods include application of spectral and/or image masks for automatically separating ambiguous or unclassifiable spectral data from valid spectral data. The '723 patent improves the accuracy of tissue classification, in part, by properly identifying and accounting for spectral data from tissue regions that are affected by an obstruction and/or regions that lie outside a diagnostic zone of interest.
Yet another example can be found in U.S. Pat. No. 7,248,909 issued to Lee et al. Lee shows device and method utilizes a broadband diffuse optical spectroscopy (DOS) system to dynamically calculate the concentrations of multiple chromophores in vivo using a non-invasive probe. The device and method permit dynamic monitoring of multiple in vivo tissue chromophores non-invasively with sensitivities necessary for effective therapeutic monitoring. The device includes a probe containing first and second source optical fibers as well as first and second detector optical fibers. The probe is placed adjacent to a sample of interest and detects reflected light which is passed to a proximally located detector and spectrometer. The concentrations of multiple chromophores are determined in real time. In an example, the multiple tissue chromophores include at least two of methemoglobin (MetHb), deoxyhemoglobin (Hb-R), oxyhemoglobin (Hb-O2), water (H2O), and methylene blue (MB). The device and method can be used quantify and monitor methemoglobin formation in subjects suffering from methemoglobinemia.
Faupel et al. also discloses another example in the U.S. Pat. No. 6,975,899. The '899 patent teaches an apparatus and method to combine more than one optical modality (spectroscopic method), including fluorescence, absorption, reflectance, polarization anisotropy, and phase modulation, to decouple morphological and biochemical changes associated with tissue changes due to disease, and thus to provide an accurate diagnosis of the tissue condition.
Another example can be found in U.S. Pat. No. 6,697,652. The '652 patent utilize a plurality of spectroscopic techniques to measure characteristics of tissue useful in the diagnosis of disease. Fluorescence, reflectance and light scattered spectra can be measured and processed to determine the size, distribution and/or composition of tissue. The methods and systems can be used particularly in the early detection of carcinoma within tissue in vivo and in vitro.
Yet another example is shown in U.S. Pat. No. 5,785,658 issued to Benaron et al. Benaron teaches a tool for nondestructive interrogation of the tissue including a light source emitter and detector which may be mounted directly on the surgical tool in a tissue contacting surface for interrogation or mounted remotely and guided to the surgical field with fiber optic cables. The light source may be broadband and wavelength differentiation can be accomplished at the detector via filters or gratings, or using time, frequency, or space resolved methods. Alternatively, discrete monochromatic light sources may be provided which are subsequently multiplexed into a single detector by time or by frequency multiplexing. The optical sensing elements can be built into a surgical tool end effector tip such as a tissue-grasping tool which has cooperating jaws (bivalve or multi-element). In an example, the light source (or the fiber optic guide) mounted on one jaw and the detector (or fiber optic guide) is mounted in the opposing jaw so that the light emitter and detector are facing one another either directly (i.e., on the same optical axis when the tool is closed) or acutely (i.e., with intersecting optical axes so that the light emitted is detected). In this case, the sensor is working in a transmission modality. Arrangements with the optical components mounted on the same member of a single member or a multi member structure, operating in a reflective modality, are disclosed.
Finally, United States Patent Application Publication number 20070054339 teaches methods that are provided for detecting biomolecular interactions. The use of labels is not required and the methods can be performed in a high-throughput manner. The '339 application also relates to optical devices.
However, for all of the technologies mentioned above, a surgeon cannot evaluate the surgical specimen until the procedure is completed and prostate extracted. Though intraoperative frozen section pathologic analysis of a few select tissue fragments from the prostate or surgical site can be obtained, it is time consuming and costly. Concrete conclusions based on such samples are unreliable, as they do not reflect the entire surgical margin status.
Therefore, a technology and technique are needed to interrogate the tumor percutaneously that reduces the false negative rate associated with needle biopsy and that assesses the surgical margin in real time to confirm complete surgical excision would reduce the number of patients undergoing surgery for small kidney or masses while improving the surgical outcome of those who do. A technology that can reduce unnecessary surgery for benign tumors and the incidence of positive surgical margins would significantly reduce kidney tumor surgery and recurrence/progression rates after surgery.
As such, it would also be highly desirable to develop an integrated optical spectroscopic method that will allow the surgeon in real time to detect prostate adenocarcinoma both on the surface of the prostate and a few millimeters beneath the surface for accurate excision of the gland during laparoscopic prostatectomy. Such a technology that can reduce the incidence of positive surgical margins would significantly reduce prostate cancer recurrence and progression rates after surgery.
The present inventors recognize these needs, and the present invention overcomes the disadvantages of the above-mentioned technologies.